An automated cell culture apparatus

Abstract

The application discloses an automatic cell culture equipment, and relates to the technical field of high-end equipment manufacturing for cell culture. The automatic cell culture equipment comprises an external closed cabinet body, a horizontal sealing partition is arranged in the external closed cabinet body, the horizontal sealing partition separates the internal space of the external closed cabinet body into a clean operation area at the upper part and an electrical control area at the lower part, the electrical control area is integrated with a control unit, a plurality of multi-axis collaborative robots and an experimental execution system which are cooperatively controlled by the control unit are arranged in the clean operation area, and the experimental execution system comprises a material temporary storage module, an experimental operation cabin module and a culture cabin module which are sequentially arranged in the horizontal direction. The plurality of multi-axis collaborative robots are arranged in the material temporary storage module, the experimental operation cabin module and the culture cabin module respectively, and are used for transferring required materials. The automatic cell culture equipment is a novel automatic equipment which is highly integrated, fully closed and capable of solving micro-operation problems.

Description

Technical Field

[0001] This application relates to the field of high-end equipment manufacturing technology for cell culture, and more specifically, to an automated cell culture device. Background Technology

[0002] With the rapid development of cell therapy technology, stringent requirements have been placed on the degree of automation, standardization of operation, and pollution control capabilities of the cell culture process, necessitating the realization of closed-loop management of the entire process from consumable storage and experimental operation to cell culture.

[0003] Existing automated cell culture equipment is either functionally limited, only able to complete part of the process (such as simple pipetting or simple culture), or lacks integration, with poor physical isolation between modules (such as consumable storage, experimental operation, and culture), posing a risk of cross-contamination. This leads to the following prominent problems with existing technical solutions: First, the low-temperature consumable storage and retrieval mechanism is poorly designed, using hinged doors or drawers, causing the refrigeration chamber to be frequently exposed to room temperature, affecting the activity and stability of biological reagents; second, the precision of handling micro-precipitates is insufficient, traditional pipetting mechanisms cannot identify the distribution of precipitates at the bottom of centrifuge tubes, resulting in a precipitate loss rate as high as 15%-20% during aspiration; third, the multi-specification consumable gripping system is complex, requiring 3-5 types of dedicated end effectors to adapt to different shaped consumables such as culture plates, centrifuge tubes, and reagent bottles, increasing equipment costs by more than 30%, and the gripper replacement process is prone to introducing contamination risks; finally, multi-module integration presents a contradiction between sealing and maintenance, with existing equipment either using an overall sealed design that requires shutdown and disassembly for individual module maintenance, or using an open structure that sacrifices isolation, failing to balance contamination control and maintenance convenience.

[0004] Therefore, those skilled in the art urgently need to find a highly integrated, fully closed-loop automated cell culture device that can solve the aforementioned microscopic operational challenges. Summary of the Invention

[0005] The main objective of this application is to provide an automated cell culture device, which is a novel automated device that is highly integrated, fully closed-loop, and capable of solving microscopic operational challenges.

[0006] To achieve the above objectives, this application proposes an automated cell culture device, including an externally enclosed cabinet. A horizontally sealed partition within the cabinet divides the internal space into an upper clean operating area and a lower electrical control area. The electrical control area integrates a control unit. The clean operating area houses several multi-axis collaborative robots and an experimental execution system, all controlled by the control unit. The experimental execution system includes a material storage module, an experimental operation chamber module, and a culture chamber module arranged sequentially along a horizontal direction. The material storage module includes: a storage box with an access port for storing materials required for room temperature or refrigerated cell culture; and a door for opening and closing the access port. The experimental operation chamber module... The module includes: a vessel platform configured to support and secure experimental vessels; a capping mechanism located above the capping station of the vessel platform, configured to automatically open or close the caps of the experimental vessels on the vessel platform; a supernatant aspiration device for aspirating the supernatant from the centrifuged cell suspension; a pipetting module located above the vessel platform, comprising multiple independently controlled liquid handling units with different capacity settings; a culture chamber module including: a cell counter and / or a carbon dioxide incubator; and a centrifuge for centrifuging the cell suspension; wherein, several multi-axis collaborative robots are respectively located in the material storage module, the experimental operation chamber module, and the culture chamber module for transferring the required materials.

[0007] Furthermore, the material storage module also includes a transfer compartment located between the storage box and the experimental operation compartment module. A multi-axis collaborative robot within the material storage module is housed in the transfer compartment. The transfer compartment includes: a consumable conveyor line with consumable trays for holding centrifuge tubes and / or cell culture plates, which can be movably extended into the experimental operation compartment module; a room temperature storage tray for holding centrifuge tubes; and a weighing module for weighing the centrifuge tubes in the material storage module and / or the room temperature storage tray.

[0008] Furthermore, the material storage module also includes: a linkage assembly, which is symmetrically arranged on both sides of the door, and the linkage assembly is connected to the storage box and the door respectively; and a drive unit, the output end of which is connected to the linkage assembly; wherein, the linkage assembly is configured to: under the drive of the drive unit, through the angle change between each linkage, drive the door to open relative to the pick-up and put-out port and perform translational lifting and lowering motion in the vertical plane.

[0009] Furthermore, the vessel platform includes: a support frame for storing centrifuge tubes of different sizes; a horizontal axis module installed at the bottom of the support frame for driving the entire vessel platform to move horizontally; and an electric gripper array arranged on the platform surface of the vessel platform, wherein the electric gripper array includes multiple rows of grippers with adjustable clamping force, the grippers being used to clamp and fix centrifuge tubes of different sizes.

[0010] Furthermore, the supernatant aspiration device includes: a support clamping unit for supporting the experimental vessel containing the centrifuged sample; an attitude adjustment unit connected to the support clamping unit for driving the experimental vessel to adjust its spatial attitude; and a visual observation unit located on one side of the experimental vessel for capturing real-time images of the precipitate distribution during the rotation of the experimental vessel.

[0011] Furthermore, the attitude adjustment unit includes: a tilt drive mechanism, which is mounted on a fixed base, with the output shaft of the tilt drive mechanism located in the horizontal direction; and a rotation drive mechanism, which is mounted on the drive end of the tilt drive mechanism; wherein the tilt drive mechanism can drive the rotation drive mechanism to tilt back and forth around the axis of the output shaft.

[0012] Furthermore, the visual observation unit includes a backlight assembly and an image acquisition device. The backlight assembly is used to provide transmitted illumination, and the acquisition end of the image acquisition device is positioned facing the bottom area of ​​the experimental vessel.

[0013] Furthermore, the experimental operation chamber module also includes a microscopic observation and picking device, which includes: a microscope module, which includes an inverted microscope body and an imaging camera mounted on the microscope body; a displacement stage, which is mounted above the inverted microscope body and configured to carry and move the cell culture plate in a horizontal plane; a light source system, which includes a main focused light source and an auxiliary diffuse reflection light source, the main focused light source being rotatably suspended above the displacement stage, and the auxiliary diffuse reflection light source being fixedly set beside the displacement stage; and an infrared needle calibration module, which is located on the displacement stage. The infrared needle calibration module is electrically connected to a control unit, which is used for communication with the displacement stage and the pipetting module. The infrared needle calibration module has two sets of orthogonally arranged infrared emitting and receiving devices, which are used to form orthogonal infrared beams in the X-axis and Y-axis directions, respectively.

[0014] Furthermore, the main focusing light source includes a rotary drive motor and a main light source module located at the drive end of the rotary drive motor. The rotary drive motor is used to drive the main light source module to rotate around the axis of the rotary drive motor by a preset angle to avoid the pipetting module.

[0015] Furthermore, the end effector of the multi-axis collaborative robot is constructed as a multi-compatible electric gripper, which includes: a fixed base for connecting to the robotic arm of the multi-axis collaborative robot; an electric push rod mounted on the fixed base; and two gripping arms connected to the electric push rod and moving in opposite directions. Each gripping arm has, along the height direction from top to bottom, the following features on its inner working surface: a horizontal groove adapting to the thickness of the cell culture plate edge; a V-shaped groove adapting to the cylindrical surface of the centrifuge tube; and an inwardly snapping claw for hooking the flange of the cup.

[0016] The technical solutions provided by the embodiments of this application may include the following beneficial effects: In this application, 1) the external enclosed cabinet and horizontal sealed partition physically isolate the clean operating area from the electrical control area, effectively preventing dust and electromagnetic interference from electrical components from contaminating the cell culture environment, thereby improving the cleanliness of the culture environment. 2) Multiple modules (material storage module, experimental operation chamber module, and culture chamber module) are arranged horizontally in sequence and transported by a multi-axis collaborative robot, shortening the material transfer path and reducing operation waiting time, thereby effectively improving the continuity of the experimental process. 3) The experimental operation chamber module integrates functions such as opening the lid, pipetting, and aspirating supernatant, realizing the automated integration of key cell culture operations, thereby reducing the risk of contamination caused by manual intervention. 4) The material storage module's dual-mode storage of room temperature / refrigeration can meet the storage needs of different materials and ensure reagent activity. 5) The control unit's coordinated control of each module enables the equipment to automate the entire process from material preparation to cell culture within a compact space, improving experimental efficiency and the stability of culture results. Attached Figure Description

[0017] The accompanying drawings, which form part of this application, are used to provide a further understanding of the application and to make other features, objects, and advantages of the application more apparent. The illustrative embodiments and descriptions of this application are used to explain the application and do not constitute an undue limitation of the application. In the drawings: Figure 1 This is a front view of the automated cell culture equipment provided in this application, wherein the figure is a view rotated 90° to the right. Figure 2 for Figure 1 A top view schematic diagram of the automated cell culture equipment shown. Figure 3 for Figure 1 The diagram shows the structure of the material storage module in the automated cell culture equipment. Figure 4 for Figure 3 The diagram shown is a front view of the material temporary storage module. Figure 5 for Figure 4 The diagram shows the structure of the material temporary storage module along the AA direction; Figure 6 for Figure 4 The diagram shows a side view of the material storage module. Figure 7 for Figure 1 The diagram shows the structure of the experimental operation chamber module of the automated cell culture equipment. Figure 8 for Figure 7 The diagram shows a top view of the vessel stage of the experimental operation chamber module, with the illustration rotated 90° to the right. Figure 9 for Figure 7 The diagram shows a right-side side view of the experimental operation cabin module. Figure 10 for Figure 7 The diagram shows a schematic left-side view of the experimental operation cabin module. Figure 11 for Figure 10 The diagram shows a top view of the experimental operation cabin module. Figure 12 for Figure 8 The diagram shows the structure of the supernatant suction device. Figure 13 for Figure 12 The diagram shows a partial structural schematic of the supernatant suction device. Figure 14 A schematic diagram of the microscopic observation and picking device of the automated cell culture equipment provided in this application; Figure 15 for Figure 14 The diagram shows a front view of the microscopic observation picking device. Figure 16 for Figure 15 The diagram shown is a top view of the structure of the microscopic observation picking device. Detailed Implementation

[0018] To enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present application, and not all embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative effort should fall within the scope of protection of the present application.

[0019] It should be noted that the terms "first," "second," etc., in the specification, claims, and accompanying drawings of this application are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate for the embodiments of this application described herein. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion; for example, a process, method, system, product, or apparatus that comprises a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such processes, methods, products, or apparatus.

[0020] In this application, the terms "upper," "lower," "left," "right," "front," "rear," "top," "bottom," "inner," "outer," "middle," "vertical," "horizontal," "lateral," and "longitudinal" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. These terms are primarily for the purpose of better describing this application and its embodiments, and are not intended to limit the indicated device, element, or component to having a specific orientation, or to be constructed and operated in a specific orientation.

[0021] Furthermore, in addition to indicating location or positional relationship, some of the aforementioned terms may also have other meanings. For example, the term "above" may also be used in some cases to indicate a certain dependency or connection relationship. Those skilled in the art can understand the specific meaning of these terms in this application based on the specific circumstances.

[0022] Furthermore, the terms "installation," "setup," "equipped with," "connection," "linked," and "socketing" should be interpreted broadly. For example, "connection" can be a fixed connection, a detachable connection, or an integral structure; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, or an internal connection between two devices, components, or parts. Those skilled in the art can understand the specific meaning of the above terms in this application according to the specific circumstances.

[0023] Figure 1 and Figure 2 The structure of the automated cell culture apparatus 100 provided according to this application is shown. (See diagram below.) Figure 1 and Figure 2 As shown, the automated cell culture equipment 100 includes an external enclosed cabinet (not shown in the figure). A horizontal sealed partition is provided inside the external enclosed cabinet. The peripheral edge of the horizontal sealed partition is sealed to the inner wall of the external enclosed cabinet. The horizontal sealed partition isolates the internal space of the external enclosed cabinet into an upper clean operating area 101 and a lower electrical control area 102. The electrical control area 102 integrates a control unit. The clean operating area 101 contains several multi-axis collaborative robots 200 and an experimental execution system, all controlled by the control unit. The experimental execution system includes material storage modules 10 arranged sequentially along the horizontal direction. Figures 3 to 6 As shown), Experimental Operation Module 20 ( Figures 7 to 13(As shown) and the culture chamber module 30, wherein: the material storage module 10 includes: a storage box 11 with a pick-and-place port 111 for storing materials required for cell culture at room temperature or refrigeration (e.g., standard reagent bottles or centrifuge tubes); a door 12 for opening and closing the pick-and-place port 111; the experimental operation chamber module 20 includes: a vessel stand 21 configured to support and fix experimental vessels (e.g., centrifuge tubes); and a lid opening mechanism 22 located above the lid opening position of the vessel stand 21. The system is configured to automatically open or close the lids of experimental glassware on the glassware stand 21; a supernatant aspirator 23 for aspirating the supernatant from the centrifuged cell suspension; a pipetting module 24 located above the glassware stand 21, comprising multiple independently controlled liquid handling units with different capacity settings; a culture chamber module 30 including a cell counter 31 and / or a carbon dioxide incubator 32; and a centrifuge 33 for centrifuging the cell suspension. Several multi-axis collaborative robots 200 are respectively located within the material storage module 10, the experimental operation chamber module 20, and the culture chamber module 30 for transporting the required materials.

[0024] In practical use, the automated cell culture equipment 100 according to an embodiment of the present invention involves manually placing a single blood collection tube into the automated cell culture equipment 100 through a transfer window. Before the experiment begins, the culture process parameters are preset by the control unit, and the door 12 of the material storage module 10 automatically opens. The multi-axis collaborative robot 200 removes the blood collection tube and the materials required for cell culture from the storage box 11 and transfers them to the vessel table 21 of the experimental operation chamber module 20 and fixes them in place. The capping mechanism 22 performs an automatic capping operation, and the pipetting module 24 calls the corresponding volume level liquid processing unit to complete the reagent addition and cell suspension preparation according to the experimental requirements. The prepared cell suspension is transferred by the multi-axis collaborative robot 200 to the centrifuge 33 for centrifugation. After centrifugation, the sample is transferred to the supernatant aspiration device 23, and the supernatant is accurately aspirated by adjusting the posture. The processed sample is transferred by the multi-axis collaborative robot 200 to the culture chamber module 30, where the cell density is detected by the cell counter 31, and then transferred to the carbon dioxide incubator 32 for culture. During the experiment, the control unit coordinates the working sequence of each module in real time to ensure the smooth execution of material transfer, experimental operations, and cultivation processes.

[0025] With the above-described configuration, the automated cell culture device 100 according to an embodiment of the present invention has the following advantages: 1) The external enclosed cabinet and horizontal sealed partition physically isolate the clean operating area from the electrical control area, effectively avoiding the pollution of the cell culture environment by dust and electromagnetic interference generated by electrical components, thereby improving the cleanliness of the culture environment.

[0026] 2) Multiple modules (material storage module 10, experimental operation chamber module 20 and culture chamber module 30) are arranged in sequence along the horizontal direction and cooperate with the multi-axis collaborative robot 200 for transportation, which shortens the material transfer path and reduces the operation waiting time, thereby effectively improving the continuity of the experimental process.

[0027] 3) The experimental operation chamber module 20 integrates functional units such as opening the lid, pipetting, and aspirating the supernatant, realizing the automated integration of key cell culture operations, thereby reducing the risk of contamination caused by manual intervention.

[0028] 4) The material temporary storage module 10 has a dual-mode storage setting of room temperature / refrigeration, which can meet the storage needs of different materials and ensure the activity of reagents.

[0029] 5) The control unit's coordinated control of each module enables the equipment to automate the entire process from material preparation to cell culture within a compact space, improving experimental efficiency and the stability of culture results.

[0030] Furthermore, in this application, the material storage module 10, the experimental operation chamber module 20, and the culture chamber module 30 each include an independent inner chamber. Between two adjacent inner chambers, mutually cooperating raised sealing ribs and recessed sealing grooves are respectively processed on their mutually close vertical end faces, and strip-shaped sealing material is provided between the raised sealing ribs and the recessed sealing grooves to form a lateral sealing connection.

[0031] Furthermore, in this application, the automated cell culture equipment 100 adopts at least a two-layer control architecture, including an upper-layer main control computer based on a first operating system and a lower-layer device control unit based on a programmable logic control unit. The upper-layer main control computer and the lower-layer device control unit communicate via industrial Ethernet. The lower-layer device control unit is electrically connected to the motor drivers, sensors, valves, and control components involved in the various modules within the automated cell culture equipment 100. Specifically: The linkage and control chain of this application consists of two layers: the upper layer is a main control computer based on a Windows system or embedded system, responsible for human-computer interaction, process flow analysis, and task scheduling. The lower layer is an equipment control unit based on a programmable logic control unit (PLC), which, as described below, is responsible for the real-time control and status acquisition of all motors (servo motors, stepper motors), sensors (temperature, weight, vision, current), valves, and lighting components involved in all modules. The main control computer and the PLC communicate via industrial Ethernet. Each module is connected to the PLC via a fieldbus (such as EtherCAT or Profibus) or an I / O module. The PLC monitors the motor current, door limit switches, weighing data, etc., involved in each module in real time, and uploads the status information to the main control computer, while simultaneously receiving and executing action commands from the main control computer.

[0032] Furthermore, in this application, at least one fan filter unit (preferably three, corresponding to the material storage module 10, the experimental operation chamber module 20, and the culture chamber module 30) is installed on the top of the external enclosed cabinet (which may be a cubic cabinet structure) for vertically injecting clean air into the clean operating area. The front of the external enclosed cabinet is provided with a human-machine interface, which includes a first touch screen connected to the upper-level main control computer and a second interactive screen connected to the lower-level equipment control unit.

[0033] In this application, the liquid processing unit is a pipette or a syringe, which has an adjustable range piston pump or syringe structure inside, so as to achieve liquid processing at different volume levels by changing the piston stroke.

[0034] Please refer to Figure 1 and Figure 2 Furthermore, the material storage module 10 is also equipped with a transfer chamber 40, which is located between the storage box 11 and the experimental operation chamber module 20. The multi-axis collaborative robot 200 in the material storage module 10 is located in the transfer chamber 40. The transfer chamber 40 includes: a consumable conveying line 41 with a consumable tray 411 on it, the consumable tray 411 is used to place centrifuge tubes and / or cell well plates, and the consumable tray 411 extends movably into the experimental operation chamber module 20; a room temperature temporary storage tray 42, which is used to place centrifuge tubes; and a weighing module 43, which is used to weigh the centrifuge tubes in the material storage module 10 and / or the room temperature temporary storage tray 42.

[0035] In this embodiment, at the start of the experiment, the control unit drives the transfer chamber 40 to start, and the multi-axis collaborative robot 200 takes centrifuge tubes and / or cell culture plates (according to preset requirements) from the storage box 11 and places them on the consumable tray 411 of the consumable conveying line 41. The consumable tray 411 automatically extends along the track to a designated position within the experimental operation chamber module 20 to complete the material transfer. For centrifuge tubes or blood collection tubes that need to be temporarily stored or stored at room temperature, the multi-axis collaborative robot 200 transfers them to the room temperature temporary storage tray 42. Before the materials are used, the weighing module 43 weighs the corresponding materials to ensure that the material specifications meet the experimental requirements. After the weighing is completed, the multi-axis collaborative robot 200 transfers the materials to the experimental operation station (within the experimental operation chamber module 20).

[0036] Through the above setup, the transfer chamber 40 achieves automated material transfer between the temporary storage area and the operating area via the consumable conveyor line 41, avoiding long-distance movement of the multi-axis collaborative robot 200 across modules, thereby shortening material transfer time and improving system operating efficiency. The ambient temperature temporary storage tray 42 provides temporary storage space for centrifuge tubes, reducing the impact of frequent retrieval on the material temporary storage module 10 and ensuring material storage stability. The weighing module 43 allows for pre-processing and testing of materials before experiments, avoiding experimental errors caused by inconsistent material specifications and improving the reliability of experimental results.

[0037] Please refer to Figures 3 to 6 Furthermore, the material storage module 10 also includes: a linkage assembly 13, which is symmetrically arranged on both sides of the door 12, and the linkage assembly 13 is connected to the storage box 11 and the door 12 respectively; and a drive unit 14, the output end of which is connected to the linkage assembly 13; wherein, the linkage assembly 13 is configured to: under the drive of the drive unit 14, drive the door 12 to open relative to the pick-up and put-down port 111 and perform translational lifting and lowering motion in the vertical plane through the angle change between each linkage.

[0038] According to the material storage module 10 of the embodiment of the invention, in the automated cell culture process, when materials need to be stored or retrieved, the drive unit 14 receives a control signal and starts, driving the linkage assemblies 13 on both sides of the door 12 to move through the transmission structure. The linkage assemblies 13, through coordinated changes in the angles between the links, allow the door 12 to rise smoothly in the vertical direction to open the retrieval port 111, allowing operators or robotic arms to store or retrieve materials through the retrieval port 111. After the operation is completed, the drive unit 14 reverses the drive of the linkage assemblies 13, lowering the door 12 in the vertical direction to the closed position, ensuring that the internal environment of the storage box 11 remains stable.

[0039] Through the above-described configuration, this application achieves vertical translation and lifting of the door 12 via the cooperation of the linkage assembly 13 and the drive unit 14, effectively reducing the horizontal space occupied by traditional door opening methods and better adapting to the compact layout requirements of automated equipment. Furthermore, the symmetrically arranged linkage assembly 13 ensures smooth and unobstructed movement of the door 12, thereby improving the reliability and service life of the mechanism and supporting the efficient advancement of automated cell culture processes.

[0040] Please refer to Figures 4 to 6 Furthermore, each of the linkage assemblies 13 symmetrically arranged on both sides of the door 12 may include a first linkage 131 and a second linkage 132 arranged in parallel. The two ends of the first linkage 131 and the second linkage 132 are respectively hinged to the side wall of the storage box 11 and the door 12. The first linkage 131 and the second linkage 132 are of equal length and remain parallel. Under the drive of the drive unit 14, the first linkage 131 and the second linkage 132 swing synchronously.

[0041] In this embodiment, when the automated cell culture equipment is running and materials need to be stored or retrieved, the drive unit 14 is activated, causing the first connecting rod 131 and the second connecting rod 132 on both sides of the door 12 to move synchronously. Since the two connecting rods are of equal length and always remain parallel, the door 12 moves smoothly vertically under their influence, thus opening the retrieval port 111. After the operator or robotic arm completes the material storage or retrieval, the drive unit 14 reverses its direction, causing the first connecting rod 131 and the second connecting rod 132 to lower the door 12 vertically, closing the retrieval port 111 and ensuring a stable internal environment within the storage box 11. It should be noted that the door 12, driven synchronously by the first connecting rod 131 and the second connecting rod 132, moves vertically along an arc trajectory within the vertical plane, maintaining a vertical posture, and a clearance space is reserved above the retrieval port 111 to allow for the arc trajectory of the door 12.

[0042] Through the above configuration, by employing parallel connecting rods 131 and 132 of equal length to form a parallelogram linkage structure (including the door 12 and the storage box 11), the door 12 maintains a vertical translational state during movement, preventing the door 12 from tilting or swaying and affecting the sealing performance of the retrieval port 111. The symmetrically arranged connecting rod assemblies 13 distribute the force on the door 12, reducing the load on individual connection points and improving the stability and service life of the mechanism. Simultaneously, the vertical translational opening method reduces the space occupied around the equipment, better suiting the compact layout requirements of automated equipment.

[0043] Please refer to Figure 5 Furthermore, the drive unit 14 may include: a servo motor 141, which is located inside the top of the storage box 11; a reduction gearbox 142, which is connected to the servo motor 141 and is used to provide power under the drive of the servo motor 141; and a synchronous belt drive mechanism 143, which is used to connect the reduction gearbox 142 with the first link 131 or the second link 132 to synchronously drive the swing angle of the link.

[0044] In this embodiment, during the operation of the automated cell culture equipment, when materials need to be stored or retrieved, the control unit sends an operation command to the drive unit 14. Upon receiving the command, the servo motor 141 inside the top of the storage box 11 starts and transmits power to the synchronous belt drive mechanism 143 via the connected reduction gearbox 142. The synchronous belt drive mechanism 143 drives either the first link 131 or the second link 132 to swing. Under the synergistic action of the parallelogram linkage assembly 13, this drives the door 12 to move vertically up and down, thus opening and closing the retrieval port 111. After the operation is completed, the servo motor 141 reverses its rotation, resetting the linkage assembly 13 via the reduction gearbox 142 and the synchronous belt drive mechanism 143, precisely closing the door 12.

[0045] With the above configuration, the drive unit 14 employs a power output method combining a servo motor 141 and a reduction gearbox 142, providing stable driving torque and ensuring smooth and reliable movement of the door 12. The synchronous belt drive mechanism 143 enables precise power transmission, effectively ensuring the synchronization of the linkage's swing angle and preventing tilting or jamming of the door 12 during lifting. The servo motor 141's placement within the top of the storage box 11 saves external space, making the overall structure more compact and adaptable to the space utilization requirements of automated cell culture equipment.

[0046] In a preferred embodiment, such as Figure 5 As shown, both the servo motor 141 and the gearbox 142 can be configured as a single unit. The gearbox 142 has a drive shaft coaxially arranged on opposite sides. The synchronous belt drive mechanism 143 includes a driving synchronous pulley, a driven synchronous pulley, and a synchronous belt wound between the two pulleys. The driving synchronous pulley is sleeved on both ends of the drive shaft, and the driven synchronous pulley is located at the hinge point of the two first connecting rods 131 and connected to the two first connecting rods 131 through a rotating shaft, so as to drive the connecting rod to swing around its hinge point.

[0047] In this embodiment, when the automated cell culture equipment needs to perform material storage and retrieval operations, the control unit sends a command to the drive unit 14. The servo motor 141 starts and transmits power to the coaxial drive shafts on both sides via the reduction gearbox 142. The drive shafts drive the active synchronous pulleys at both ends to rotate synchronously. The active synchronous pulleys drive the driven synchronous pulleys to rotate via synchronous belts, which in turn drives the two first linkages 131 connected to the driven synchronous pulleys to swing around their hinge points. Under the cooperative action of the parallelogram linkage assembly 13, the door 12 achieves vertical translation and lifting movements, completing the opening and closing of the retrieval port 111. After the operation is completed, the servo motor 141 rotates in reverse, resetting each component through the aforementioned transmission path.

[0048] With the above configuration, a single servo motor 141 and a reduction gearbox 142, along with a coaxial transmission shaft, can simultaneously drive the synchronous belt transmission mechanisms 143 on both sides, ensuring the synchronicity of the movement of the connecting rod assemblies 13 on both sides of the door 12 and preventing the door 12 from tilting during lifting. The transmission cooperation between the active and driven synchronous belt pulleys enables precise power transmission, thereby ensuring the consistency of the connecting rod swing angle and improving the smoothness of the door 12's movement. Furthermore, this drive structure has a compact layout, reducing the number of parts, lowering the assembly complexity and maintenance costs of the equipment, while also contributing to improved reliability and service life of the mechanism.

[0049] Furthermore, the material storage module 10 may be equipped with an indexing turntable (not shown in the figure) driven by a stepper motor, and the indexing turntable may be equipped with multiple positioning slots for placing centrifuge tubes.

[0050] In this embodiment, before the experiment, centrifuge tubes can be placed into the positioning slot of the indexing turntable of the material storage module 10 according to a preset specification through the opening and closing mechanism on the outside of the external enclosed cabinet. The control unit starts the stepper motor according to the experimental procedure instructions, driving the indexing turntable to rotate to the material picking station (picking and placing port 111). The multi-axis collaborative robot 200 picks up the centrifuge tubes according to the position coordinates of the positioning slot. After picking up the centrifuge tubes, the indexing turntable automatically rotates to the next material picking station. When materials need to be replenished, centrifuge tubes can be replenished through the opening and closing mechanism on the outside of the external enclosed cabinet.

[0051] With the above settings, the indexing turntable achieves precise indexing and positioning through stepper motor drive, ensuring that the centrifuge tubes are picked up in the same position, thus improving the accuracy and efficiency of the multi-axis collaborative robot 200's grasping.

[0052] Please refer to Figures 7 to 11 Furthermore, the vessel platform 21 may include: a support frame 211 for storing centrifuge tubes of different sizes; a horizontal axis module 212 installed at the bottom of the support frame 211 for driving the entire vessel platform 21 to move horizontally; and an electric gripper array 213 arranged on the platform of the vessel platform 21, wherein the electric gripper array 213 includes multiple rows of grippers with adjustable clamping force, and the grippers are used to clamp and fix centrifuge tubes of different sizes.

[0053] In this embodiment, the multi-axis collaborative robot 200 places centrifuge tubes one by one into one or more rows of grippers in the electric gripper array 213, and the grippers close and lock the tube body.

[0054] Through the above configuration, the combination of the support frame 211 and the electric gripper array 213 enables the classified storage and stable clamping of centrifuge tubes of different specifications, avoiding instability caused by differences in vessel size. The horizontal movement function driven by the horizontal axis module 212, combined with the multi-station layout, shortens the transfer path of centrifuge tubes between operating units, improving the overall operating efficiency of the system. The adjustable clamping force ensures the positional accuracy of centrifuge tubes during operation while avoiding damage to vessels caused by over-clamping, enhancing the system's adaptability to diverse experimental needs.

[0055] Please continue to refer to Figures 7 to 11 Furthermore, the vessel stand 21 may also include a disposable gun tip storage assembly 25, which includes a storage bracket and a plurality of disposable gun tips disposed on the storage bracket.

[0056] In this embodiment, before the experiment, different models of disposable pipette tips are placed in the storage rack according to specifications. When the instrument stage 21 moves to the pipetting station, the pipetting module drives the corresponding Z-axis unit to descend according to a preset program, and the automatic loading and unloading is completed through the interference fit between the pipette tip and the pipetting head. After use, the disposable pipette tips are moved by the pipetting module to the designated waste collection area for detachment and collection.

[0057] Through the above settings, a disposable nozzle storage component 25 is integrated, which automates the retrieval of disposable nozzles and avoids the risk of contamination introduced by manual nozzle loading and unloading.

[0058] Please refer to Figures 7 to 11 In some embodiments, the cap opening mechanism 22 may include a lifting module 221 and a rotary electric gripper 222 disposed on the lifting module 221. When performing the cap opening action, the rotary electric gripper 222 is configured to clamp the cap and move upward in the vertical direction with the lifting module 221 while applying rotational torque. The rotary electric gripper 222 is also configured to continue to hold the cap after the cap is opened and move upward with the lifting module 221 to transfer the cap to a temporary storage position.

[0059] In this embodiment, the multi-axis collaborative robot 200 places centrifuge tubes one by one into one or more rows of grippers in the electric gripper array 213, and the grippers close and lock the tube body. Subsequently, the horizontal axis module 212 is activated, advancing the entire container platform 21 forward so that the centrifuge tube opening is precisely aligned with the capping mechanism 22 above. When the container platform 21 transfers the centrifuge tube to the capping station, the lifting module 221 drives the rotating electric gripper 222 to descend vertically to the cap position. After the gripper closes and clamps the cap, it moves upward with the lifting module 221 while applying rotational torque to complete the opening action. After the cap is opened, the rotating electric gripper 222 maintains the clamping state and continues to move upward with the lifting module 221 to a preset temporary storage height. After the centrifuge tube completes subsequent operations, the lifting module 221 drives the gripper to move downward and rotate in the opposite direction to close the cap.

[0060] Through the above settings, the coordinated action of the rotating electric gripper 222 and the lifting module 221 realizes the integrated operation of opening the tube cap and vertical lifting, avoiding the risk of sample contamination or splashing inside the tube that may occur when opening the cap manually.

[0061] In this application, the capping mechanism 22 also includes a horizontal displacement module, with a lifting module 221 mounted on the moving part of the horizontal displacement module, enabling the capping mechanism 22 to also function as a centrifuge tube transfer device. Specifically, after the centrifuge tube is capped, the rotary electric gripper 222 maintains a stable grip on the centrifuge tube, and the horizontal displacement module transfers the centrifuge tube from the capping station to the target processing station (such as a supernatant aspiration device or a pipetting area). Upon reaching the target station, the rotary electric gripper 222 releases the centrifuge tube and returns to its initial position, awaiting the next operation command. In this way, the capping, capping, and transfer operations are completed through the same mechanism, shortening the transfer time of the centrifuge tube between different stations and improving the overall efficiency of the experimental process.

[0062] Please refer to Figure 12 and Figure 13 Furthermore, the supernatant aspiration device 23 may include: a support clamping unit 231 for supporting the experimental vessel containing the centrifuged sample; an attitude adjustment unit 232 connected to the support clamping unit 231 for driving the experimental vessel to adjust its spatial attitude; and a visual observation unit 233 located on one side of the experimental vessel for capturing real-time images of the precipitate distribution during the rotation of the experimental vessel.

[0063] In this application, it is understood that the supernatant aspiration device 23 further includes: a control unit controlling the liquid processing unit in the pipetting module 24 to aspirate the supernatant from the centrifuged cell suspension.

[0064] In practical use, the supernatant aspiration device 23 according to an embodiment of the present invention places the centrifuge tube after centrifugation in the support clamping unit 231. The attitude adjustment unit 232 is activated by the control unit to first tilt the centrifuge tube to a set angle so that the supernatant naturally accumulates on one side. Then, while the centrifuge tube is slowly rotated, the vision observation unit 233 continuously acquires bottom images. The control unit automatically determines the angle position where the precipitate is most concentrated by analyzing the distribution characteristics of the precipitate in the image, and then rotates the centrifuge tube to that angle and fixes it. Finally, the long-stroke pipette tip of the liquid processing unit, guided by the control unit, accurately extends into the bottom of the centrifuge tube near the supernatant enrichment area to complete the automated aspiration of the supernatant.

[0065] Through the above-described configuration, this application achieves precise positioning of trace precipitates via coordinated control of posture adjustment and visual recognition, avoiding the problem of aspiration angle deviation caused by experience differences in manual operation. The long-stroke pipette tip, combined with the tilting enrichment of centrifuge tubes, ensures sufficient aspiration of supernatant while minimizing disturbance to the precipitate, effectively reducing the risk of sample loss. The entire operation is completed automatically within a closed system, reducing manual intervention and improving the consistency and reproducibility of experimental operations. It also reduces the possibility of cross-contamination, making it particularly suitable for cell culture experiments requiring high precision and cleanliness.

[0066] Please refer to Figure 12 and Figure 13 Furthermore, the attitude adjustment unit 232 may include: a tilt drive mechanism 2321, which is disposed on a fixed foundation and the output shaft of the tilt drive mechanism 2321 is located in the horizontal direction; and a rotation drive mechanism 2322, which is disposed at the drive end of the tilt drive mechanism 2321; wherein the tilt drive mechanism 2321 can drive the rotation drive mechanism 2322 to tilt back and forth around the axis of the output shaft.

[0067] In this application, the control unit is configured to control the tilting drive mechanism 2321 to tilt the centrifuge tube to a preset angle so that the supernatant is concentrated at a low point on one side of the centrifuge tube. It is also configured to control the rotation drive mechanism 2322 to rotate the centrifuge tube and trigger the visual observation unit 233 to continuously capture images of the bottom of the centrifuge tube.

[0068] In this embodiment, the centrifuge tube after centrifugation is fixed to the support clamping unit 231. The control unit first activates the tilting drive mechanism 2321 to tilt the centrifuge tube around the horizontal output shaft to a set angle, causing the supernatant to accumulate towards the lower point on one side of the centrifuge tube under the action of gravity. Subsequently, the rotation drive mechanism 2322 is controlled to slowly rotate the centrifuge tube around its own central axis, and the vision observation unit 233 is triggered to continuously acquire images of the bottom of the centrifuge tube. By analyzing the distribution characteristics of the precipitate in the images, the rotation angle where the precipitate is most concentrated is located and fixed. Finally, the long-stroke pipette tip of the liquid processing unit is guided to extend into the bottom of the centrifuge tube near the supernatant accumulation area to complete precise liquid aspiration.

[0069] Through the aforementioned setup, the coordinated control of tilt and rotation drives enables directional enrichment of the supernatant and precise positioning of the precipitate, thereby avoiding sample loss or contamination risks caused by angle judgment errors during manual operation. Furthermore, the mechanical transmission mechanism of the attitude adjustment unit 232 ensures the stability of the centrifuge tube's tilt angle and rotation position. Combined with real-time image feedback from the visual observation unit 233, this effectively improves the consistency and reliability of the liquid aspiration operation. In this application, the entire process from sample positioning to liquid aspiration can be completed without manual intervention, thus helping to reduce the probability of cross-contamination, and is particularly suitable for cell culture experiments requiring high operational precision.

[0070] Furthermore, the tilting drive mechanism 2321 may include a servo motor and an axial converter. The servo motor drives the axial converter via a synchronous belt or gear mechanism. The output shaft of the axial converter is connected to a mounting plate. The bearing clamping unit 231 is mounted on the mounting plate to drive the centrifuge tube to tilt back and forth around the axis of the output shaft.

[0071] Furthermore, the tilt angle can range from 0 to 30 degrees.

[0072] In this embodiment, the centrifuged sample tube is placed on the support clamping unit 231. The control unit activates the servo motor of the tilt drive mechanism 2321, which transmits power to the axial converter via a synchronous belt or gear mechanism, driving the mounting plate and centrifuge tube to tilt around the horizontal output shaft to the desired angle. During this process, the supernatant accumulates towards the lower point on one side of the centrifuge tube under gravity, facilitating subsequent precise aspiration. Thus, by using a servo motor in conjunction with the axial converter, stable adjustment and precise control of the centrifuge tube tilt angle are achieved, avoiding the problem of poor supernatant accumulation caused by angle deviations during manual operation.

[0073] Furthermore, the rotary drive mechanism 2322 may include a hollow rotary motor, the output shaft of which is coaxially arranged with the clamping position of the centrifuge tube. After the centrifuge tube is clamped, its upper part is located in the central through hole of the hollow rotary motor, and the output end of the hollow rotary motor cooperates with the centrifuge tube through an internal clamping mechanism to drive the centrifuge tube to rotate 360° clockwise or counterclockwise around its own central axis.

[0074] In this embodiment, the centrifuged sample tube is supported by the support clamping unit 231, and the upper part of the centrifuge tube is inserted into the central through hole of the hollow rotary motor. The motor is then connected to the outer wall of the centrifuge tube through the internal clamping mechanism. The control unit starts the hollow rotary motor, driving the centrifuge tube to rotate clockwise or counterclockwise around its central axis. Simultaneously, the vision observation unit 233 is triggered to continuously acquire images of the sediment distribution at the bottom of the centrifuge tube until the angle position where the sediment is most concentrated is located, after which the rotation stops.

[0075] Through the above-described configuration, employing a hollow rotary motor and coaxial clamping mechanism, 360° rotation of the centrifuge tubes is achieved without dead angles. Combined with the internal clamping mechanism, this ensures the stability of the centrifuge tubes during rotation, thus preventing sediment distribution shifts caused by eccentric rotation. The central through-hole structure not only meets the axial positioning requirements of the centrifuge tubes but also provides space for upper liquid transfer operations, making the collaborative work between the rotary drive and the liquid processing unit more compact and efficient, and contributing to improved accuracy in locating trace sediments.

[0076] Furthermore, the clamping mechanism inside the hollow rotary motor can be an elastic clamp.

[0077] In this application, during the centrifuge tube installation process, the upper part of the centrifuge tube is inserted into the central through hole of the hollow rotary motor. The elastic clamp naturally opens under radial pressure and fits tightly against the outer wall of the centrifuge tube, forming an adaptive clamping fixation. In this way, by using the elastic clamp as a clamping mechanism, the adaptive clamping of centrifuge tubes of different diameters is achieved by utilizing its own elastic deformation characteristics, avoiding the risk of centrifuge tube damage that may be caused by rigid clamping.

[0078] Please refer to Figure 13 Furthermore, the visual observation unit 233 may include a backlight assembly and an image acquisition device, wherein the backlight assembly is used to provide transmitted illumination, and the acquisition end of the image acquisition device is positioned facing the bottom area of ​​the experimental vessel.

[0079] In this embodiment, after the centrifuge tube has been tilted, the backlight assembly is activated to provide transmitted illumination, creating a clear contrast between the sediment at the bottom of the centrifuge tube and the background. The control image acquisition device is aimed at the bottom area of ​​the centrifuge tube, and continuously captures images of the sediment distribution as the centrifuge tube rotates due to the rotation drive mechanism 2322. These images are then analyzed by the control unit to locate the angle where the sediment is most concentrated.

[0080] The above-described configuration, employing a backlight assembly for transmissive illumination, effectively enhances the contrast between the sediment and the bottom of the centrifuge tube, thus avoiding glare interference that may occur with traditional top lighting. The image acquisition device is oriented precisely towards the bottom area, ensuring the stability and clarity of image acquisition during rotation. This provides a reliable visual basis for the control unit to accurately identify the sediment distribution, helping to improve the accuracy of subsequent liquid aspiration operations.

[0081] Furthermore, the backlight assembly can be an LED backlight panel, and the image acquisition device can be an industrial camera (e.g., a CCD industrial camera). The LED backlight panel and the industrial camera are respectively positioned on opposite sides of the bottom of the centrifuge tube to provide transmitted illumination.

[0082] In this embodiment, an LED backlight panel is positioned opposite the industrial camera. The high stability and uniform illumination of the LED light source ensure consistent imaging of the precipitate. The industrial camera's professional image acquisition capabilities, combined with the lateral lighting path, effectively reduce interference from reflections from the centrifuge tube wall, improving the clarity of the precipitate outline.

[0083] Please refer to Figures 14 to 16 Furthermore, the experimental operation chamber module 20 may also include a microscopic observation and picking device 50, which includes: a microscope module 51, which includes an inverted microscope body 511 and an imaging camera 512 mounted on the microscope body 511; a displacement stage 52, which is mounted above the inverted microscope body 511 and configured to carry and move the cell culture plate in a horizontal plane; and a light source system, which includes a main focused light source 531 and an auxiliary diffuse reflection light source 532, wherein the main focused light source 531 is rotatably suspended above the displacement stage 52. A diffuse reflection light source 532 is fixedly installed on the side of the displacement stage 52; an infrared needle calibration module 54 is installed on the displacement stage 52. The infrared needle calibration module 54 is electrically connected to the control unit. The control unit is used to communicate with the displacement stage 52 and the pipetting module 24 (which can be understood as being electrically connected to the control unit (such as a PLC or industrial computer) respectively, and to perform signal processing and closed-loop control through the control unit). The infrared needle calibration module 54 is equipped with two sets of orthogonally arranged infrared emitting and receiving devices, which are used to form orthogonal infrared beams in the X-axis direction and the Y-axis direction respectively.

[0084] In practical use, the microscopic observation and picking device 50 according to an embodiment of the present invention places the cell culture plate on the displacement stage 52, and calibrates the pipette tip in the X and Y axes using the infrared needle calibration module 54. After calibration, the displacement stage 52 is controlled to move the culture plate to the microscope observation area. The main focusing light source 531 is rotated to a suitable angle according to observation needs, or the auxiliary diffuse light source 532 is turned on to provide ambient illumination, and the imaging camera 512 acquires cell images. When it is necessary to pick target cells, the pipetting module 24 moves to the calibrated target position, and the pipette tip is controlled to complete the cell aspiration operation. In this application, the system controls the movement of the displacement stage 52, scans with the microscope module 51, identifies and locates target cell patches with a diameter of approximately 0.3 mm, and moves them to the center of the field of view. This application also includes a routine observation process: for routine observations that do not require picking, the multi-axis collaborative robot 200 directly places the cell culture plate on the displacement stage 52. The system controls the displacement stage 52 to move along a preset path. The microscope is used to scan each well of the cell culture plate in sequence and take pictures to record the cell growth status. After completion, the multi-axis collaborative robot 200 retrieves the cell culture plate and puts it back into the incubator.

[0085] Through the above-described configuration, the microscopic observation and picking device 50 according to this embodiment of the invention employs orthogonal infrared beam calibration, enabling dual-dimensional verification of the pipette tip positioning accuracy, thereby improving the accuracy of cell picking. The combination of the rotatable structure of the main focusing light source 531 and the auxiliary diffuse reflection light source 532 can adapt to the observation needs of different cell types and enhance imaging clarity. The coordinated control of the displacement stage 52 and the pipetting module 24 reduces manual intervention, thereby effectively reducing operational errors and providing stable and reliable technical support for automated cell culture processes.

[0086] Furthermore, the displacement stage 52 may include an X-axis translation mechanism and a Y-axis translation mechanism. The X-axis translation mechanism is disposed on the moving part of the Y-axis translation mechanism. The X-axis translation mechanism and the Y-axis translation mechanism are used to drive the cell culture plate to translate along the X-axis direction and the Y-axis direction.

[0087] In this embodiment, after the cell culture plate is fixed to the displacement stage 52, the control unit drives the Y-axis translation mechanism for coarse positioning based on the target well coordinates, and then completes the precise positioning through the X-axis translation mechanism, moving the target well to the center of the microscope observation area. After completing the operation at the current well position, the X-axis translation mechanism and the Y-axis translation mechanism work together to move the culture plate sequentially to the next target well position along a preset path, realizing continuous processing of multiple well positions.

[0088] By adopting the above settings and using a hierarchical arrangement of X-axis and Y-axis translation mechanisms, the culture plate can be moved precisely in two dimensions in the horizontal plane, thus improving the positioning accuracy of well position switching.

[0089] Please continue to refer to Figures 14 to 16 Furthermore, the main focusing light source 531 may include a rotary drive motor 5311 and a main light source module disposed at the drive end of the rotary drive motor 5311. The rotary drive motor 5311 is used to drive the main light source module to rotate around the axis of the rotary drive motor by a preset angle to avoid the pipetting module 24.

[0090] In this embodiment, during cell observation, the main focusing light source 531 is at a preset illumination angle to provide focused light for the microscope. When the pipetting module 24 needs to enter the operating area, the rotary drive motor 5311 drives the main light source module to rotate around the axis of the rotary drive motor to an avoidance angle (e.g., 90 degrees). After the pipetting operation is completed, it is reset to the original illumination angle.

[0091] Through the above settings, the angle adjustment of the main light source module driven by the rotary drive motor 5311 is achieved, thus avoiding spatial interference between the light source and the pipetting module 24 and avoiding the limitations on the operation path imposed by traditional fixed light sources. The dynamic switching setting of the light source angle not only ensures the illumination quality during the observation stage but also provides ample working space for pipetting operations, improving the overall operational smoothness and structural compactness of the device.

[0092] Furthermore, the auxiliary diffuse light source 532 can be constructed as a semi-circular structure, with the diffuse reflection irradiation surface of the auxiliary diffuse light source 532 facing the center of the microscopic field of view on the displacement stage 52.

[0093] In this embodiment, when performing cell observation or picking operations, the auxiliary diffuse light source 532 is turned on. Its semi-circular diffuse irradiation surface can uniformly illuminate the central area of ​​the microscopic field of view on the displacement stage 52 from the side. It is used in conjunction with the main focused light source 531 to optimize the cell imaging effect, or to provide ambient lighting separately when the main focused light source 531 rotates to avoid it.

[0094] Through the above configuration, the semi-circular structure enables the auxiliary diffuse light source 532 to provide surround illumination to the center of the microscopic field of view from multiple angles, reducing shadows and light spot interference caused by traditional point light source illumination and improving the detail clarity of cell images. The arrangement of the diffuse illumination surface facing the center of the field of view ensures that the illumination energy is concentrated in the observation area, reducing energy consumption while meeting imaging requirements. This complements the main focused light source 531, enhancing the device's adaptability to different cell types and culture environments.

[0095] Furthermore, the infrared beams generated by the two sets of infrared transmitting and receiving devices in the infrared alignment module 54 are in the same horizontal height range and have a preset beam width W in the Z-axis direction.

[0096] In this embodiment, before the pipette tip performs the cell picking operation, the pipetting module 24 is controlled to drive the pipette tip to pass through the infrared beams in the X-axis and Y-axis directions in sequence. When the beam is blocked, the infrared receiver generates a trigger signal. The system calculates the actual coordinate offset of the pipette tip in the horizontal plane according to the signal interruption position, and calibrates the positioning parameters of the pipette tip accordingly.

[0097] Through the above settings, the orthogonal infrared beam setup within the same horizontal plane enables synchronous calibration of the pipette tip in the X and Y axes, avoiding planar positioning deviations that may occur with traditional single-axis calibration. The preset beam width can adapt to the calibration requirements of pipette tips of different sizes, ensuring stable detection even for small-diameter pipette tips, improving the compatibility and reliability of the calibration process, and providing a fundamental guarantee for high-precision cell picking.

[0098] In the above embodiments of this application, specifically, two symmetrically orthogonally arranged infrared transmitting and receiving devices, i.e., infrared sensors, are used to form infrared beams in the X and Y directions, respectively. Utilizing the physical width characteristics of the infrared beams (possessing detectable left and right boundary interruption trigger points), no additional sensors are required. Specific triaxial calibration method: 1) X-axis calibration. Using the initial reference starting point of the needle as a reference, control the horizontal bidirectional movement of the needle: move left to capture the left boundary interruption coordinate X1 of the beam; move right to detach from the beam, and then move right again to capture the right boundary interruption coordinate X2 of the beam; calculate the beam center point by arithmetic mean: X0=(X1+X2) / 2; calculate the X-axis offset based on the displacement difference between the reference starting point and X0.

[0099] 2) Z-axis calibration. Move the needle to the center point X0 obtained from the X-axis calibration; lift it along the positive Z-axis until the needle leaves the infrared beam; probe downwards along the negative Z-axis to capture the interruption coordinate Z0 of the first triggered beam, and combine this with the known preset beam width W of the infrared beam, using the formula Z... 中心 = Z0 + W / 2 The center coordinate of the beam in the Z direction is calculated as Z0 + W / 2. 中心 ; with Z 中心 Using Z0 as the reference, calculate the Z-axis offset.

[0100] 3) Y-axis calibration. It employs the same dual-boundary interrupt sampling + midpoint calculation logic as the X-axis, relying on orthogonal infrared beams in the Y direction to calculate the Y-axis offset.

[0101] 4) Overall needle alignment. By adding and subtracting the three-axis offsets, overall compensation of the three-axis coordinates is completed, realizing automatic needle alignment closed loop.

[0102] Please return Figures 7 to 11 Furthermore, the pipetting module 24 may also include an independently configured Z-axis drive module, which is used to drive the pipetting head to move up and down in the vertical direction so that the tip of the pipetting head cuts vertically downward into or out of the horizontal plane where the orthogonal infrared beam is located.

[0103] In this embodiment, during infrared needle calibration, the Z-axis drive module drives the pipette tip to descend vertically, causing the tip to cut into the horizontal plane containing the orthogonal infrared beams along the axial direction. After calibration, the Z-axis drive module drives the pipette tip to rise vertically, withdrawing its tip from the horizontal plane. During cell picking, the Z-axis drive module precisely controls the pipette tip's ascent and descent based on the target well depth, completing the liquid aspiration and release actions.

[0104] Through the above configuration, the independent Z-axis drive module enables independent vertical control of the pipette tip, ensuring that its tip can vertically enter or exit the infrared beam plane, avoiding interference with calibration accuracy caused by horizontal movement. The vertical lifting mechanism allows for precise control of the insertion depth when the pipette tip is operating within the orifice, reducing disturbance to the cell culture environment. Simultaneously, in conjunction with the horizontal displacement mechanism, it achieves precise positioning in three-dimensional space, improving the stability and reliability of automated operation.

[0105] Furthermore, the end effector of the multi-axis collaborative robot 200 is constructed as a multi-compatible electric gripper, which includes: a fixed base for connecting to the robotic arm of the multi-axis collaborative robot 200; an electric push rod disposed on the fixed base; and two gripping arms connected to the electric push rod and moving in opposite directions. Each gripping arm has, along the height direction from top to bottom, the following features on its inner working surface: a horizontal groove adapted to the thickness of the cell culture plate edge; a V-shaped groove adapted to the cylindrical surface of the centrifuge tube; and an inwardly snapping claw for hooking the flange of the cup.

[0106] In this embodiment, the multi-axis collaborative robot 200 calls the corresponding gripping mode through the control unit according to the type of material to be gripped: when transporting cell culture plates, the robotic arm adjusts to align the horizontal groove with the edge of the culture plate, and the electric push rod drives the gripping arm to move in opposite directions, using the horizontal groove to clamp the edge of the culture plate to complete the gripping; when transporting centrifuge tubes, it switches to the V-shaped groove position, and the self-centering function of the V-shaped structure achieves stable gripping of the centrifuge tubes; for cups with flanges, the robotic arm moves down so that the inner-locking claw hooks onto the flange of the cup, and the slight closing action of the gripping arm completes the hook-and-hold gripping. During the gripping process, the control unit automatically adjusts the gripping force according to the weight of the material to avoid excessive squeezing that could cause deformation of the experimental vessel or leakage of contents.

[0107] Through the above-described configuration, the multi-compatible electric gripper, with its integrated horizontal groove, V-groove, and internal clamping jaws, enables one-stop gripping of various experimental vessels such as cell culture plates, centrifuge tubes, and flanged cups. This eliminates the need for frequent end effector replacements, significantly reducing downtime for gripper changes and improving the continuity of experimental procedures. The thickness-adaptive design of the horizontal grooves ensures uniform force distribution during culture plate gripping, preventing edge deformation. The self-centering characteristic of the V-groove improves the centering of centrifuge tubes, reducing the risk of shaking during transport. The internal clamping jaws enhance the gripping stability of flanged vessels through a dual fixation of hooking and clamping. The modular connection between the fixed base and the robotic arm facilitates future maintenance and replacement, while also reducing the overall manufacturing cost of the equipment.

[0108] In this application, a flexible silicone pad is also attached to the inner side of each gripping arm. The drive motor of the multi-compatible electric gripper has a built-in current sensor, and the signal output terminal of the current sensor is electrically connected to the control unit of the multi-axis collaborative robot 200. In this application, the lower-level device control unit monitors the real-time operating current of the drive motor of the multi-compatible electric gripper in real time. When performing a gripping action, if the real-time operating current remains below the no-load threshold, the lower-level device control unit determines that the gripping has failed and triggers an alarm. When performing a movement action, if the real-time operating current momentarily exceeds the stall threshold, the lower-level device control unit determines that the movement path is obstructed, controls the drive motor to stop the current movement, and simultaneously sends an alarm message to the upper-level main control computer.

[0109] It should be noted that any components or equipment not detailed in this application are made using existing equipment or instruments that can be directly applied to assist in achieving a complete cell culture technology solution.

[0110] In summary, the specific working principle and operating logic of the automated cell culture device 100 according to embodiments of the present invention can be, for example, as follows: Taking the fully automated processing flow of a single cell sample as an example, the working principle of the automated cell culture device 100 of this embodiment of the invention is explained as follows: 1) Initial material preparation: A single blood collection tube is manually placed into the automated cell culture equipment 100 through a transfer window, which is usually located in the transfer chamber 40. The control unit initiates the process and sends instructions to the PLC. The PLC controls the multi-axis collaborative robot 200 in the transfer chamber 40, first driving its multi-compatibility gripper to grab centrifuge tubes or reagent bottles from the material storage module 10. At this time, the PLC first controls the drive unit of the linkage assembly to rotate forward, quickly and vertically lifting the door 12 a short distance (just enough to allow the reagent bottle to pass through) through the parallelogram linkage. After the multi-axis collaborative robot 200 picks up the bottle, the drive unit immediately reverses, and the door 12 quickly falls to press the sealing strip and close, greatly shortening the cold chamber exposure time.

[0111] 2) Delivery and Verification: The multi-axis collaborative robot 200 sequentially places single blood collection tubes, centrifuge tubes, culture plates, etc., picked up from the room temperature zone onto the through-type consumable delivery line 41. These tubes can also be placed on the weighing module 43 for weight verification. The verification data (actual weight) is compared with the preset standard weight of the consumables; if the difference exceeds the tolerance range, an alarm is triggered. Simultaneously, this weight is recorded as a margin reference. The consumable delivery line 41 transports these items to the entrance of the experimental operation cabin module 20, where they are received by the multi-axis collaborative robot 200 within the experimental operation cabin module 20.

[0112] 3) Core operations of the experimental operation chamber module 20 (taking supernatant aspiration as an example): Centrifuge tubes that have undergone centrifugation are transferred by a multi-axis collaborative robot 200 to the station of the suction supernatant device 23 and inserted into the bearing clamping unit.

[0113] Step 1: The PLC controls the hollow rotary motor to start, causing the centrifuge tube to rotate slowly and uniformly 360 degrees. Simultaneously, the side-mounted industrial camera is triggered to capture continuous or fixed-point images. The images are transmitted to the PLC or host computer for real-time analysis, identifying the arc-shaped interface formed by the sediment at the bottom of the tube, and calculating the tube rotation angle θ1 that makes this interface clearest and most complete.

[0114] Step 2: The PLC controls the tilting drive mechanism to drive the tilting shaft, causing the centrifuge tube to tilt forward or backward by a preset angle θ2 (e.g., 20 degrees), so that the supernatant gathers in the lower part of the bottom of the centrifuge tube. The purpose of tilting is to ensure that the pipette tip adheres to the tilted centrifuge tube wall for aspiration, avoiding the removal of cells from the bottom.

[0115] Step 3: Based on the calculated position of the precipitate (angle θ1) and the tilt angle θ2, the control unit calculates the three-dimensional spatial path that the pipette tip needs to enter (avoiding the precipitate area and penetrating from the side of the tube wall enriched with supernatant). The command is sent to the PLC, which controls the Z-axis long-stroke pipette module 24 to drive the slender pipette tip down along the predetermined path until the tip reaches the predetermined depth at the bottom of the tube. Then, negative pressure is initiated to aspirate the supernatant. The camera can monitor the aspiration process in real time.

[0116] 4) Anomaly Handling and Protection: During any of the grasping or moving processes described above, the control unit and PLC of the multi-axis collaborative robot 200 continuously monitor the real-time operating current of the gripper motor. If the current remains below the no-load threshold during the grasping action, it is determined that the "no-load grasp" has failed; if the current spikes instantly during movement, exceeding the stall threshold, it is determined that the movement path is obstructed. Once such an anomaly is detected, the PLC will immediately cut off the power to the motor and urgently stop the relevant action within milliseconds. At the same time, it will send a high-priority alarm message to the host computer, triggering the system to enter a safety hold state, awaiting manual intervention.

[0117] 5) Closed-loop culture and daily monitoring: After treatment, the cells are seeded onto culture plates and delivered to a CO2 incubator by a multi-axis collaborative robot 200. During the culture cycle, which can last for several tens of days, the control unit periodically instructs the multi-axis collaborative robot 200 to remove specific culture plates from the culture chamber and transport them to the experiment according to a preset schedule.

[0118] It should be noted that the steps shown in the flowchart in the accompanying drawings can be executed in a computer system such as a set of computer-executable instructions, and although a logical order is shown in the flowchart, in some cases the steps shown or described may be executed in a different order than that shown here.

[0119] Obviously, those skilled in the art should understand that the various units or steps of this application described above can be implemented using general-purpose computing devices. They can be centralized on a single computing device or distributed across a network of multiple computing devices. Optionally, they can be implemented using computer-executable program code, thereby storing them in a storage device for execution by a computing device, or fabricating them separately as individual integrated circuit modules, or fabricating multiple modules or steps into a single integrated circuit module. Thus, this application is not limited to any particular combination of hardware and software.

[0120] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. An automated cell culture device, characterized in that, The system includes an externally enclosed cabinet with a horizontally sealed partition that divides the internal space of the cabinet into an upper clean operating area and a lower electrical control area. The electrical control area integrates a control unit. The clean operating area contains several multi-axis collaborative robots and an experimental execution system, all controlled by the control unit. The experimental execution system includes a material storage module, an experimental operating chamber module, and a culture chamber module arranged sequentially along a horizontal direction. The material storage module includes: a storage box with an access port for storing materials required for cell culture at room temperature or under refrigeration; and a door for opening and closing the access port. The experimental operation chamber module includes: a vessel platform configured to support and fix experimental vessels; a capping mechanism located above the capping station of the vessel platform, configured to automatically open or close the caps of the experimental vessels on the vessel platform; a supernatant aspiration device for aspirating the supernatant from the centrifuged cell suspension; and a pipetting module located above the vessel platform, comprising multiple independently controlled liquid handling units with different capacity settings. The culture chamber module includes: a cell counter and / or a carbon dioxide incubator; and a centrifuge for centrifuging the cell suspension. The plurality of multi-axis collaborative robots are respectively located in the material storage module, the experimental operation chamber module, and the culture chamber module for transferring the required materials.

2. The automated cell culture equipment according to claim 1, characterized in that, The material storage module also includes a transfer compartment, which is located between the storage box and the experimental operation module. A multi-axis collaborative robot within the material storage module is housed in the transfer compartment, which includes: A consumables delivery line is provided with a consumables tray for placing centrifuge tubes and / or cell well plates, and the consumables tray extends movably into the experimental operation chamber module; A room temperature temporary storage tray, on which centrifuge tubes are placed; A weighing module is used to weigh the centrifuge tubes in the material storage module and / or the room temperature storage tray.

3. The automated cell culture equipment according to claim 1, characterized in that, The material temporary storage module also includes: A linkage assembly is symmetrically arranged on both sides of the door body, and the linkage assembly is connected to the storage box and the door body respectively; The drive unit, the output of which is connected to the linkage assembly; The linkage assembly is configured such that, driven by the drive unit, the door opens relative to the pick-up / placement opening and performs a translational lifting and lowering motion in the vertical plane by changing the angle between the linkages.

4. The automated cell culture equipment according to claim 1, characterized in that, The vessel stand includes: Support frame, which is used to store centrifuge tubes of different sizes; A horizontal axis module, which is installed at the bottom of the support frame, is used to drive the entire vessel platform to move horizontally. An electric gripper array is arranged on the table surface of the vessel platform, and the electric gripper array includes multiple rows of grippers with adjustable clamping force, the grippers being used to clamp and fix centrifuge tubes of different specifications.

5. The automated cell culture equipment according to claim 1, characterized in that, The supernatant suction device includes: The support clamping unit is used to hold experimental vessels containing centrifuged samples; An attitude adjustment unit, which is connected to the bearing clamping unit, is used to drive the experimental vessel to adjust its spatial attitude. A visual observation unit is installed on one side of the experimental vessel to capture real-time images of the distribution of the precipitate during the rotation of the experimental vessel.

6. The automated cell culture equipment according to claim 5, characterized in that, The attitude adjustment unit includes: A tilting drive mechanism is mounted on a fixed foundation, and the output shaft of the tilting drive mechanism is located in the horizontal direction. A rotary drive mechanism is disposed at the drive end of the tilt drive mechanism; The tilting drive mechanism can drive the rotary drive mechanism to tilt back and forth around the axis of the output shaft of the tilting drive mechanism.

7. The automated cell culture equipment according to claim 5, characterized in that, The visual observation unit includes a backlight assembly and an image acquisition device. The backlight assembly is used to provide transmitted illumination, and the acquisition end of the image acquisition device is positioned facing the bottom area of ​​the experimental vessel.

8. The automated cell culture equipment according to claim 1, characterized in that, The experimental operation chamber module also includes a microscopic observation picking device, which comprises: A microscope module comprising an inverted microscope body and an imaging camera mounted on the microscope body; A displacement stage is mounted above the inverted microscope body and configured to support and move the cell culture plate in a horizontal plane. The light source system includes a main focusing light source and an auxiliary diffuse reflection light source. The main focusing light source is rotatably suspended above the displacement stage, and the auxiliary diffuse reflection light source is fixedly disposed on the side of the displacement stage. An infrared needle alignment module is mounted on the displacement stage. The infrared needle alignment module is electrically connected to the control unit. The control unit is used to communicate with the displacement stage and the pipetting module. The infrared needle alignment module is equipped with two sets of orthogonally arranged infrared emitting and receiving devices, which are used to form orthogonal infrared beams in the X-axis direction and the Y-axis direction, respectively.

9. The automated cell culture equipment according to claim 8, characterized in that, The main focusing light source includes a rotary drive motor and a main light source module located at the drive end of the rotary drive motor. The rotary drive motor is used to drive the main light source module to rotate around the axis of the rotary drive motor by a preset angle to avoid the pipetting module.

10. The automated cell culture equipment according to claim 1, characterized in that, The end effector of the multi-axis collaborative robot is configured as a multi-compatible electric gripper, which includes: A fixed base for connecting to the robotic arm of the multi-axis collaborative robot; An electric actuator is mounted on the fixed base; Two clamping arms are connected to the electric push rod and move in opposite directions; Each of the clamping arms has the following features on its inner working surface along the height direction from top to bottom: a horizontal groove to accommodate the thickness of the cell culture plate edge, a V-shaped groove to accommodate the cylindrical surface of the centrifuge tube, and an inner snap-fit ​​claw for hooking the flange of the cup.

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